Amylase, Lipase, and Acute Pancreatitis in People With Type 2 Diabetes Treated With Liraglutide: Results From the LEADER Randomized Trial

Background

Liraglutide, a GLP-1 analogue, is an established therapy for type 2 diabetes mellitus (T2DM), however, it has been associated with increased levels of serum lipase and amylase, as well as a potential for an increased risk of acute pancreatitis [1-4]. In the LEADER trial, 9,340 T2DM patients at cardiovascular risk were randomized to liraglutide or placebo, on top of standard of care, and followed for 3.5–5.0 years [5].

In this analysis, the effects of liraglutide treatment on serum lipase and amylase and the number of cases of acute pancreatitis were evaluated in the LEADER study. Levels were measured each 6 months.

Main results

In the liraglutide arm, elevated levels of lipase and amylase were seen 6 months after initiation of treatment, and persisted for the duration of the study.

Similarly, an estimated 7.0% (1.07; 95% CI: 1.06–1.09; P<0.001) increase in amylase was seen with an observed amylase change from 59.4 units/L to 70.9 units/L for liraglutide.

In the liraglutide group, 51.3% of patients had at least one time an elevated lipase level compared with 31.8% in the placebo group.

In the liraglutide group, 8.3% of patients and in the placebo group 5.3% had lipase increases of threefold or more.

29.0% of liraglutide-treated patients and 22.9% in the placebo group had at least one time an elevated amylase level during the study.

1.0% of liraglutide-treated patients and 0.8% in the placebo group had amylase levels elevated by threefold or more.

0.4% of patients in the liraglutide group and 0.5% of patients in the placebo group had an acute pancreatitis event that was confirmed by adjudication.

The corresponding event rates were 1.1/1,000 PYO (patient years of observation) for the liraglutide group and 1.7/1,000 PYO for the placebo group.

89.5% of pancreatitis cases in the liraglutide group and 83.9% of cases in the placebo group had mild acute pancreatitis events, according to the modified Atlanta criteria.

In both treatment arms, most cases of acute pancreatitis developed >12 months after the initiation of the study.

In both the liraglutide and placebo groups, there was no association between onefold or threefold elevated lipase and the subsequent risk of acute pancreatitis in patients without acute pancreatitis at the time of measurement.

Conclusion

In the LEADER study, numerically fewer events of acute pancreatitis were observed in the liraglutide group compared with the placebo group. Liraglutide increased serum amylase and lipase levels, but these elevations were not predictive of the development of acute pancreatitis in asymptomatic T2DM patients.